Maternal antibiotic treatment peripartum has differential consequences on protein expression of intestinal cytoprotective heat shock proteins in her offspring

Background: Peripartum antibiotics are thought to have negative consequences on intestinal barrier function, immune system development and long-term health. These effects might be related to disturbances in neonatal bacterial colonization. Protective heat shock proteins 25 and 72 are induced physiologically by luminal bacteria in cultured intestinal epithelial cell (IEC) and in mouse intestine. HSP60 has been recently shown to contribute to IEC protection in vitro but data in vivo are lacking. We aimed at testing the hypothesis that early alterations in gut microbial colonization impact intestinal cytoprotective HSPs. Methods: Sows received amoxicillin orally (40mg/kgBW/d, ATBQ n=11; vs. untreated CTL, n=12) around parturition (d-10 till d+21). Offspring (1/litter) were sacrificed during the suckling period (d14, d28) and after weaning (d42), and ileal tissues were collected. HSP27, HSP60, HSP70 and cognate HSC70, as well as the transcription factor HSF1 were determined bywestern blotting and tissue levels expressed relative to β-actin. Enzyme activity of intestinal alkaline phosphatase (IAP), an HSP-like protein crucial in the detoxification of pro-inflammatory bacterial components (e.g. LPS) was also investigated in comparison. Results: Ileal tissue levels of HSP27 in offspring were unaffected by antibiotic treatment of mothers. HSP60 tended to be (P=0.07) and HSC70 was (P,0.05) higher in offspring born to ATBQ sows than in CTL (+40 and +24%, respectively). By contrast, HSP70 was much lower in offspring born to ATBQ sows than in CTL (P,0.01) and this difference was significant (P,0.01) atday 28 (-69%) and day 42 (-59%) (treatment by age interaction, P ,0.05). Ileal protein expression of HSF1 in offspring was unaffected by ATBQ treatment of sows or offspring post-natal age. In comparison to HSPs, IAP activity displayed a treatment by time interaction: it was twice lower at day 14 in offspring born to ATBQ sows than in CTL (P ,0.01) with no differences at days 28 and 42. Conclusion: Maternal antibiotic treatment peripartum had differential consequences on protein expression of intestinal heat shock proteins in heroffspring in the swine. This did not involve the modulation of HSP-gene transcription factor HSF1, suggesting alternate regulatory mechanisms. Collectively, the data suggest complex, time-dependent interactions between colonizing maternal fecal microbiota and offspring intestinal HSP expression. Changes in offspring intestinal microbiota and long-term effects of perinatal antibiotic treatment on offspring intestinal HSP family are being investigated.